Phase I/II multisite trial of optimally dosed clofarabine and low-dose TBI for hematopoietic cell transplantation in acute myeloid leukemia.

Clofarabine is an immunosuppressive purine nucleoside analog that may have better anti-leukemic activity than fludarabine. We performed a prospective phase I/II multisite trial of clofarabine with 2 Gy total body irradiation as non-myeloablative conditioning for allogeneic hematopoietic cell transplantation in adults with acute myeloid leukemia who were unfit for more intense regimens. Our main objective was to improve the 6-month relapse rate following non-myeloablative conditioning, while maintaining historic rates of non-relapse mortality (NRM) and engraftment.

Tandem autologous/allogeneic hematopoietic cell transplantation with bortezomib maintenance therapy for high-risk myeloma.

We evaluated tandem autologous/allogeneic hematopoietic cell transplantation followed by bortezomib maintenance therapy in a prospective phase 2 trial of treatment of high-risk multiple myeloma. The high-dose conditioning regimen for autologous hematopoietic cell transplantation consisted of melphalan 200 mg/m. The nonmyeloablative conditioning regimen for the allogeneic transplant involved low-dose total body irradiation (2 Gy) with or without fludarabine (30 mg/m × 3 days).

Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial.

The risks and benefits of adding fludarabine to a 2-Gy total body irradiation (TBI) nonmyeloablative regimen are unknown. For this reason, we conducted a prospective randomized trial comparing 2-Gy TBI alone, or in combination with 90 mg/m(2) fludarabine (FLU/TBI), before transplantation of peripheral blood stem cells from HLA-matched related donors. Eighty-five patients with hematological malignancies were randomized to be conditioned with TBI alone (n = 44) or FLU/TBI (n = 41).

Non-myeloablative allogeneic haematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: a multicentre experience.

Patients with relapsed diffuse large B-cell lymphoma (DLBCL) who have failed or are ineligible for autologous haematopoietic cell transplantation (HCT) have a poor prognosis. We examined the outcomes of non-myeloablative allogeneic HCT in this setting. Thirty-one patients with DLBCL and one patient with Burkitt lymphoma received allogeneic HCT following 2 Gy total body irradiation with or without fludarabine.

Diminishing the risk of nonrelapse mortality in hematopoietic stem cell transplantation: Prediction of exposure to the cyclophosphamide metabolite carboxyethylphosphoramide mustard.

Objectives: Our objectives were (1) to develop a population pharmacokinetic model for cyclophosphamide, 4-hydroxycyclophosphamide, and carboxyethylphosphoramide mustard (a reporter for nonrelapse mortality) in hematopoietic stem cell transplantation patients and (2) to validate a Bayesian approach to dosing.

Methods: In this study 147 patients received intravenous infusions of 60 mg. kg -1.

Cyclophosphamide metabolism, liver toxicity, and mortality following hematopoietic stem cell transplantation.

Liver toxicity caused by high-dose myeloablative therapy leads to significant morbidity after hematopoietic cell transplantation. We examined the hypothesis that liver toxicity after cyclophosphamide and total body irradiation is related to cyclophosphamide through its metabolism to toxins. Cyclophosphamide was infused at 60 mg/kg over 1 to 2 hours on each of 2 consecutive days, followed by total body irradiation.